Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the mechanism mediating the rapid progression to schistosomiasis in cirrhotic patients.
Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis.
Results: On the basis of our analysis, we identified 1,144 proteins, among which 67 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with cirrhosis resulting from S. japonicum infection.
Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Our results shed new light on the molecular mechanisms that are dysregulated in and contribute to the pathogenesis of schistosomiasis-induced hepatic fibrosis. C1QA and CFD are promising diagnostic markers for patients with cirrhosis resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.

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This is a list of supplementary files associated with this preprint. Click to download.
Additional file1: Table S1. Differentially expressed proteins of serum samples between SHF with F2 and healthy controls (sheet 1). Table S2. Differentially expressed proteins of serum samples between SHF with F4 and SHF with F2 (sheet 2). Table S3. KEGG pathway analysis of the differentially expressed proteins of serum samples between SHF with F2 and healthy controls (fold change of ≥± 1.5) (sheet 3). Table S4. KEGG pathway analysis of the differentially expressed proteins of serum samples between SHF with F4 and SHF with F2 (fold change of ≥± 1.5) (sheet 4).
Additional file2: Figure S1. Overall technical route of this project. Figure S2. The qualities of the proteome dataset. (A) Quantitative heatmap of DIA. (B) The scores of Principle Component Ananlysis (PCA). (C) Chart of iRT elution time. (D) Column peak capacity statistics. (E) Protein scores of FDR. (F) The scatterplot of QC. Figure S3. Distribution analysis of differentially expressed proteins. (A) The protein ratio distribution between the healthy control individual and SHF-F2 patient serum samples. (B) The protein ratio distribution between SHF-F4 and SHF-F2 patient serum samples.
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Posted 10 Feb, 2021
On 26 Feb, 2021
Received 25 Feb, 2021
Received 16 Feb, 2021
On 09 Feb, 2021
Invitations sent on 04 Feb, 2021
On 04 Feb, 2021
Received 04 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
Posted 10 Feb, 2021
On 26 Feb, 2021
Received 25 Feb, 2021
Received 16 Feb, 2021
On 09 Feb, 2021
Invitations sent on 04 Feb, 2021
On 04 Feb, 2021
Received 04 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
On 03 Feb, 2021
Background: Schistosoma japonicum (S. japonicum) is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatuous lesions, the main pathogenic factor of schistosomiasis. Although global awareness of the association between schistosomiasis-indued hepatic fibrosis and s. japonicum infection is increasing, little is known about the mechanism mediating the rapid progression to schistosomiasis in cirrhotic patients.
Methods: We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis.
Results: On the basis of our analysis, we identified 1,144 proteins, among which 67 were differentially expressed between the healthy control and SHF-F2 groups and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). Furthermore, our results indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing patients with cirrhosis resulting from S. japonicum infection.
Conclusions: This report is the first to provide a global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Our results shed new light on the molecular mechanisms that are dysregulated in and contribute to the pathogenesis of schistosomiasis-induced hepatic fibrosis. C1QA and CFD are promising diagnostic markers for patients with cirrhosis resulting from S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals with different stages of advanced S. japonicum-induced hepatic fibrosis and might provide fundamental information for further detailed investigations.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
Additional file1: Table S1. Differentially expressed proteins of serum samples between SHF with F2 and healthy controls (sheet 1). Table S2. Differentially expressed proteins of serum samples between SHF with F4 and SHF with F2 (sheet 2). Table S3. KEGG pathway analysis of the differentially expressed proteins of serum samples between SHF with F2 and healthy controls (fold change of ≥± 1.5) (sheet 3). Table S4. KEGG pathway analysis of the differentially expressed proteins of serum samples between SHF with F4 and SHF with F2 (fold change of ≥± 1.5) (sheet 4).
Additional file2: Figure S1. Overall technical route of this project. Figure S2. The qualities of the proteome dataset. (A) Quantitative heatmap of DIA. (B) The scores of Principle Component Ananlysis (PCA). (C) Chart of iRT elution time. (D) Column peak capacity statistics. (E) Protein scores of FDR. (F) The scatterplot of QC. Figure S3. Distribution analysis of differentially expressed proteins. (A) The protein ratio distribution between the healthy control individual and SHF-F2 patient serum samples. (B) The protein ratio distribution between SHF-F4 and SHF-F2 patient serum samples.
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